Dietary
isoflavones, such as
genistein and
daidzein, are metabolised by the human gut microflora. Case-control studies have disclosed a link between the formation of the
daidzein metabolite
equol and
prostate cancer risk. We evaluated the effects of
genistein,
daidzein and five metabolites on two
prostate cancer cell lines by determining
DNA integrity and cell growth. LNCaP cells contain the T877A
androgen receptor mutation whereas Los Angeles
prostate cancer (LAPC)-4 cells express the wild-type receptor, both of which may affect responses to
isoflavones.
DNA integrity was determined using the comet assay. Cell growth was assessed by staining
DNA with 4',6'-diamidino-2-pheylindole hydrochloride. Endogenous
steroid hormones, but not
isoflavones, induced
DNA strand breaks.
Dihydrotestosterone stimulated the growth of both cell lines. 17beta-Oestradiol increased the growth of LNCaP but not LAPC-4 cells, pointing to an involvement of the T877A
androgen receptor.
Isoflavones did not stimulate growth in either
prostate cancer cell line. However, the growth of LNCaP and LAPC-4 cells was suppressed by
genistein (inhibitory concentration 50 % (IC50) 39.7 mumol/l, 37.2 mumol/l) and by
equol (IC50 53.8 mumol/l, 35.1 mumol/l).
O-desmethylangolensin inhibited the growth of LAPC-4 cells (IC50 45.2 mumol/l), but not of LNCaP cells. In conclusion,
isoflavones do not damage
DNA or promote growth of
androgen-dependent
prostate cancer cells. Several
isoflavones, including the reduced
daidzein metabolites
equol and
O-desmethylangolensin, suppress
cancer cell growth. Taken together, these data suggest a contribution of gut-formed
isoflavone metabolites to the beneficial effects of dietary
isoflavones on
prostate cancer risk.